Patients with hypertrophic cardiomyopathy (HCM) frequently have arrhythmias and hemodynamic abnormalities, and are prone to sudden death and syncope. Atrial fibrillation (AF) occurs in 15% of patients with hypertrophic cardiomyopathy (HCM) and can have serious hemodynamic consequences. We tested the hypothesis that regularization of ventricular contraction but with provision of chronotropic response to exercise by AV Node ablation and implantation of a rate-responsive ventricular demand pacemaker (VVIR) may improve symptoms and hemodynamics in patients with drug-refractory AF. Ten consecutive patients (age, 59+13 yrs; 6+2 drugs failed/patient) underwent radio-frequency (RF) AV Node ablation plus implantation of a VVIR device. All patients had baseline cardiac catheterization. At 3.2+1.3 months follow-up evaluation, symptoms were improved in all patients and medications requirements were reduced. Four patients have underwent repeat catheterization. Right heart pressures were markedly reduced in 3 patients. In addition, obstruction to flow of blood out of the left ventricle was eliminated in two patients with obstructive HCM. Thus, these preliminary findings suggest that RF ablation of the AV node plus implantation of a VVIR device may be a successful therapeutic strategy in HCM patients who are severely symptomatic and have failed to benefit from drug therapy.